Rifampin Data

Pharmacology	Rifampin, a synthetic rifamycin B derivative, inhibits DNA-dependent RNA polymerase, exerting bactericidal activity against mycobacteria, most Gram-positive bacteria, and some Gram-negative bacteria (e.g., Neisseria meningitidis). It enhances the activity of antistaphylococcal agents in refractory infections but shows in vitro antagonism with vancomycin (not clinically significant). Primary resistance is rare, but resistance develops rapidly if used alone.
Administration and Adult Dosage	- PO for latent tuberculosis infection: 10 mg/kg/day (max 600 mg) as a single dose for 4 months; or combined with pyrazinamide (see Pyrazinamide dosage) - PO or IV for active tuberculosis: 600 mg/day as a single dose with at least one other antitubercular agent (see Isoniazid dosage) - PO for meningococcal meningitis prophylaxis: 600 mg/day for 4 days or 600 mg twice daily for 2 days - PO for staphylococcal infection: 600 mg/day as a single dose with another antistaphylococcal agent
Special Populations - Pediatric Dosage	- PO for active tuberculosis (>5 yr): 10–20 mg/kg/day (max 600 mg) as a single dose with at least one other antitubercular agent - PO for meningococcal meningitis prophylaxis: • <1 month: 5 mg/kg twice daily for 2 days • 1 month–12 yr: 10 mg/kg/day (max 600 mg) for 4 days, or 10 mg/kg (max 600 mg) twice daily for 2 days
Special Populations - Geriatric Dosage	Same as adult dosage.
Other Conditions	- Hepatic dysfunction/biliary obstruction: Accumulation expected; no specific dosage guidelines - Renal impairment: No dosage adjustment needed
Dosage Forms	- Capsule: 150, 300 mg - Capsule (Rifamate): Rifampin 300 mg + isoniazid 150 mg - Tablet (Rifater): Rifampin 120 mg + isoniazid 50 mg + pyrazinamide 300 mg - Injection: 600 mg
Patient Instructions	- Take with a full glass of water on an empty stomach (1 hr before or 2 hr after meals) for best absorption - Take regularly to avoid increased toxicity - Expect harmless red-orange discoloration of sweat, tears, saliva, feces, urine; may permanently discolor soft contact lenses - Report fever, malaise, jaundice, or unusual bleeding
Missed Doses	- Take missed dose as soon as remembered; if near next dose, take only that dose, leaving ≥12 hr between doses; do not double dose
Pharmacokinetics - Serum Levels	- Adequate absorption: Peak 8–24 mg/L (10–29 µmol/L) 2 hr post 600–750 mg dose
Pharmacokinetics - Fate	- Absorption: 100% orally; peak ~10 mg/L (12 µmol/L) 1–3 hr post 600 mg dose; food delays but does not reduce bioavailability - First-pass metabolism: Significant hepatic extraction, saturated at doses >300–450 mg - Distribution: Wide; CSF penetration only with inflamed meninges; 80% plasma protein bound; Vd = 0.97 ± 0.36 L/kg - Clearance: Cl = 0.21 ± 0.1 L/hr/kg - Metabolism: Hepatic deacetylation to partially active metabolite; enterohepatic recirculation - Excretion: 50–60% in feces; 12–15% unchanged in urine
Pharmacokinetics - t¹⁄₂	- 3.5 ± 0.8 hr; increases with higher doses, may shorten after weeks of use; prolonged in liver disease/biliary obstruction
Adverse Reactions & Side Effects	Frequent: - GI symptoms (nausea, vomiting) - Asymptomatic liver enzyme elevation Rare (more with intermittent, high-dose therapy): - Acute reversible renal failure (tubular damage, interstitial nephritis), sometimes with hepatic failure - Clinical hepatitis (higher risk with pre-existing liver disease, alcoholism) - Jaundice (due to bile competition, especially with liver disease) - Thrombocytopenia, flu-like syndrome (fever, joint pain, muscle cramps)
Contraindications	- Hypersensitivity to rifamycin derivatives
Precautions & Warnings	- Use cautiously in pregnancy, lactation - Increased hepatotoxicity risk in daily alcohol users, pre-existing liver disease, or history of drug-associated hepatic damage - Monitor closely with intermittent dosing due to higher adverse reaction risk
Drug Interactions	- Potent CYP3A inducer, reducing levels of oral contraceptives, corticosteroids, cyclosporine, enalapril, HIV protease inhibitors, propranolol, methadone, metoprolol, mexiletine, phenytoin, quinidine, theophylline, tolbutamide, oral verapamil, warfarin, zidovudine; may require dose increases - Increases isoniazid metabolism to hepatotoxic metabolites
Parameters to Monitor	- Question monthly for hepatitis prodromes (fever, malaise) - Baseline and monthly AST, ALT in high-risk groups (alcoholism, liver disease); not predictive of clinical hepatitis without symptoms - Monitor for thrombocytopenia, renal function in intermittent therapy
Class and Drug Brand Name	- Class: Rifamycin Antibiotics - Brand Names: Rimactane, Rifadin, Various
Notes	- Essential in combination TB regimens to prevent resistance; rapid resistance emerges if used alone - High-level resistance seen in multi-drug-resistant TB, especially in AIDS patients - Limited role in MRSA endocarditis; use only after conventional therapy failure, with a third agent (e.g., gentamicin) to prevent resistance - Avoid routine use in non-endocarditis MRSA infections unless vancomycin fails

References

Hand of Clinical Drug Data